Insight into the effect of ibuprofen on the permeability of the membrane: a molecular dynamic simulation study

Abstract

Studying interactions between drugs and cell membranes is of great interest to designing novel drugs, optimizing drug delivery, and discerning drug mechanism action. In this study, we investigated the physical properties of the bilayer membrane model of POPC upon interaction with ibuprofen (IBU) using molecular dynamics simulations. The area per lipid (APL) was calculated to describe the effect of ibuprofen on the packing properties of the lipid bilayer. The APL was 0.58 nm² and 0.63 nm² for the membrane in low and high IBU respectively, and 0.57 nm² for the membrane without IBU. Our finding showed that the mean square deviation (MSD) increased with increased ibuprofen content. In addition, the order parameter for the hydrocarbon chain of lipids increased with increased ibuprofen content. There was an increment in the transfer free energy after the head group region while it was maximum in the hydrophobic core for hydrogen peroxide (H₂O₂) (∼6.2 kcal.mol^-1) and H₂O (∼3.4 kcal.mol^-1) which then decreased to respective values of (∼4.6 kcal.mol^-1), and (∼2.3 kcal.mol^-1) at the center of the bilayer in the presence of IBU. It seems that in the presence of ibuprofen, the free energy profile of the permeability of water and H₂O₂ significantly decreased. These findings show that ibuprofen significantly influences the physical properties of the bilayer by decreasing the packing and intermolecular interaction in the hydrocarbon chain region and increasing the water permeability of the bilayer. These results may provide insights into the local cytotoxic side effects of ibuprofen and its underlying molecular mechanisms.Communicated by Ramaswamy H. Sarma.

Keywords: Ibuprofen; a non-steroidal anti-inflammatory drug; permeability of cell membrane; potential of mean force; side effects; umbrella sampling.